EXCEED THE SPACE PROVIDED. Alaska Natives have survived extreme environmental conditions with limited food resources for thousands of years. Despite a traditional diet high in fat,Alaska Natives have evidenced little obesity, heart disease and diabetes. Recent acculturation has led to a more sedentary lifestyle, increased alcohol consumption, more smoking and a shift towards a western diet high in carbohydrates. Along with these changes in diet and lifestyle, the prevalence of obesity, diabetes, heart disease, stroke ar.dcancer is increasing in AlaskaNatives. Their suseptibility to alterations in diet may beexplained in part by the 'thrifty gsne' hypothesiswhich suggests that individuals living in a harsh environmentwith an unstable food supply enhance their probability of survival by maximizing storage of surplus energy. Identification of genes that influence energy balance in Alaska Natives is an important aspect of intervention because knowledge of relevant allelic variation allows one to prospectively evaluate an individual's risk for disease, and to assess the combined influence of environmental, nutritionaland genetic factors in the development of health problems secondary to obesity. Alaska Natives represent a unique unexplored population that may be ideal to identify genes for complex disorders like obesity because their geographic isolation, shared environment, small population size, and minimal genetic admixture have contributed to relatively greater genetic homogeniety, and presumably increased disequilibrium, when compared to other Native American populations. Since obesity is a major risk factor for the development of many diseases increasingly common among Alaska Natives, the overall goal of the proposed research is to collect essential baseline data for the successful identification of genes which may predispose Alaska Natives to obesity. This will be accomplished by: (1) identify markers, associated with obesity by DNA pooling-genome scan approaches; (2) conducting family-based linkage disequilibrium testing to assess the effects of specific candidate genes on the obesity phenotypes in Alaska Natives; and (3) hiring new faculty :hatwill expand intellectualcapital at the University of Alaska. Analysis of the genetics of obesity in Alaska Natives in collaboration with new faculty at the University of Alaska and a strong mentoring group of researchers at Columt ia University, Duke University, and the University of Alabama Birmingham will result in the development of a valuable genetic resource, as well as increase our understanding of the genetic variation and predisposition towards obesity in Native Americans.